This invention relates to the treatment of migraine headaches and more particularly to the use of scopolamine when administered in a transdermal therapeutic system which is programmed to deliver a measured quantity of scopolamine over a predetermined period of time.
Migraine is a paroxysmal disorder characterized by recurrent attacks of headache, with or without associated visual and gastroinestinal disturbances.
Etiology and Incidence: The cause of migraine is unknown, but evidence suggests a functional disturbance of cranial circulation. Prodromal symptoms (e.g. flashes of light, hemianopia, paresthesias), are probably due to intracerebral vasonconstriction, and the head pain to dilation of scalp arteries. Migraine may occur at any age but usually begins between ages 10 and 30, more often in women than in men. Remission after age 50 is not uncommon.
Symptoms and Signs: Headache may be preceded by a short period of depression, irritability, restlessness, or anorexia, and in some patients by scintillating scotomas, visual field defects, paresthesias, or (rarely) hemiparesis. These symptoms may disappear shortly before the headache appears or may merge with it. Pain is either unilateral or generalized. Symptoms usually follow a pattern in each patient, except that unilateral headaches may not always be on the same side. The patient may have attacks daily or only once in several months.
Untreated attacks may last for hours or days. Nausea, vomiting, and photophobia are common. The extremities are cold and cyanosed, and the patient is irritable and seeks seclusion. The scalp arteries are prominent, and their amplitude of pulsation is increased. Intracranial vascular malformations are a rare cause of migrainous headaches; other manifestations are seizures, cranial bruits, signs of a mass lesion, or subarachnoid hemmorhage.
Diagnosis is bases on the symptom patterns described above in a patient who shows no evidence of intracranial pathologic changes. The diagnosis is more probable with a family history of migraine or if visual prodromata occur. See The Merck Manual of Diagnosis and Therapy, fourteenth edition, 1982, p. 1299.
Previous migraine treatments have included asprin or codine to alleviate mild attacks and in severe attacks ergotamine tartrate in an amount of from 0.25 to 0.5 milligrams per dose, not to exceed 1.0 milligrams per 24 hour period, is indicated, either given by the subcutaneous, intramuscular or sublingual route of administration. Once therapy has been begun the patient is typically instructed to lie down in a quiet, dark room for at least two hours. The speed and thoroughness of the relief from pain are reported to be directly proportional to the promptness with which medication is started after the onset of an attack.
It is important, according to prior therapies, that treatment be started early, as quickly after the onset of an attack as possible. If the attack has reached its peak, larger amounts of ergotamine are required and not only is a longer time required for effective action but also unpleasant side effects from the medication are more pronounced. Depending upon the route of administration, the quantity of ergotamine administered has a definite upper limit per 24 hour period, an excess of which causes untoward, sometimes severe, side effects. While parenterally administered ergotamine may often bring prompt relief, oral medication, which is the type typically taken by a patient that is not institutionalized, requires a longer period of time to provide the degrees of relief desired, an average of 5 hours being required. Even then, according to the literature ergotamine may fail in severe attacks. For a description of contemporary therapy of migraine see Goodman and Gilman, "The Pharmacological Basis of Therapeutics", the fifth edition, pages 877-878 (1975).
Contemporary methods of therapy, particularly with use of ergotamine tartrate have numerous cautions, potential side effects and other unattractive features making an alternative, more reliable, regimen of therapy attractive.